PRoMPT BOLUS Australia and New Zealand
- Project status: Active
Research area: Clinical Sciences > Emergency
PRagMatic paediatric trial of balanced vs normal saline fluid in sepsis (PRoMPT BOLUS).
PRoMPT BOLUS is a large clinical trial that will enrol over 8,000 children with sepsis across the United States, Canada, Australia, and New Zealand.
PRoMPT BOLUS is a large clinical trial that will enrol over 8,000 children with sepsis across the United States, Canada, Australia, and New Zealand.
Overview
The goal of PRoMPT BOLUS is to compare 0.9 per cent saline and balanced fluids that are both commonly used in routine clinical care. Both fluids are helpful to treat paediatric sepsis, but we do not know which fluid is the safest and most effective.
PRoMPT BOLUS is a large pragmatic clinical trial, meaning the study conditions mimic ‘real life’ as much as possible. The study has a simple inclusion criteria, few exclusion criteria, and very few elements of care that are protocolised. PRoMPT BOLUS will enrol over 8,000 children with sepsis across the United States, Canada, Australia, and New Zealand.
Find out more about PRoMPT BOLUS:
Purpose
Approximately 2,500 children outside the newborn period die from septic shock each year in the U.S. and thousands more die worldwide. Despite widespread implementation of resuscitation protocols, contemporary studies still report 2 to 6 per cent mortality for children with septic shock treated in the paediatric ED.
Crystalloids are the standard resuscitative fluid for septic shock. 0.9 per cent saline and balanced fluids (Plasma-Lyte 148, Ringer’s Lactate, and Hartmann’s Solution) are inexpensive, stable at room temperature, and nearly universally available with identical storage volumes and dosing strategies. Notably, both are also of proven clinical benefit in septic shock.
However, 0.9 per cent saline is used in 80 to 95 per cent of cases of paediatric septic shock, despite data supporting that balanced fluid resuscitation may have superior efficacy and safety. The high chloride content of 0.9 per cent saline has been associated with acute kidney injury, acidemia, hyperkalaemia, vascular permeability, inflammation, coagulopathy, fluid overload, and death.
Balanced fluids have shown a 1 to 4 per cent absolute mortality reduction and up to 50 per cent lower odds of dialysis compared to 0.9 per cent saline in observational and non-randomised interventional studies in adult sepsis. Because definitive conclusions could not be drawn from existing observational and non-randomised studies, 0.9 per cent saline overwhelmingly remains the most commonly used fluid based on historical precedent (particularly in paediatrics).
To definitively test the comparative effectiveness of 0.9 per cent saline versus balanced fluids, a well-powered randomised controlled trial (RCT) is necessary.
Information for participants
Get involved
PRoMPT BOLUS will enrol children over six months and less than 18 years of age with possible sepsis during an emergency department visit at a study site.
Children will be considered as having possible sepsis if their doctor thinks they may have sepsis that will require treatment with both IV antibiotics and IV fluids, and their doctor is worried about possible shock.
The study will include children who are previously healthy, as well as children with chronic medical problems.
Research team
Role | Team member |
---|---|
Lead Researcher & Principal Investigator | Associate Professor Elliot Long |
Research Coordinator | Amanda Williams |
Australian and New Zealand Steering Committee | Catherine Wilson Dr Meredith Borland Dr Sarah McNab Dr Ben Gelbart Professor Ed Oakley Professor Franz Babl Professor Stuart Dalziel |
Research
Results of pilot study
The PRoMPT BOLUS Feasibility Pilot Clinical Trial was performed between January and August 2018 at the Children’s Hospital of Philadelphia. The aim was to determine the feasibility of a multi-centre, pragmatic randomised clinical trial to compare balanced and 0.9 per cent saline fluid resuscitation in children with suspected septic shock.
Eligible patients were between 6 months and 18 years-old who were treated in the emergency department for suspected septic shock, operationalised as blood culture, antibiotics, and fluid resuscitation for abnormal perfusion. The clinical team carried screening, enrolment, and randomisation out as part of routine care.
Patients were randomised to receive either lactated Ringer’s or 0.9 per cent saline for up to 48 hours following randomisation.
Other than fluid type, all treatment decisions were at the clinical team’s discretion. Feasibility outcomes were:
- Proportion of eligible patients enrolled,
- Acceptability of enrolment via the U.S. federal exception from informed consent (EFIC) regulations, and
- Adherence to randomised study fluid administration.
The key findings from this study were:
- A high proportion (85 per cent) of eligible patients were able to be enrolled.
- Families, patients, and caregivers were supportive of enrolment through EFIC, with 43 (98 per cent) of the 44 patients enrolled under EFIC agreeing to complete the study.
- Hospital staff could follow the randomisation scheme to achieve strong protocol adherence, with patients randomised to lactated Ringer’s receiving a median of only 20 per cent of study fluid as 0.9 per cent saline, compared to 99 per cent of study fluid as 0.9 per cent saline in the saline arm (absolute difference 79 per cent, 95 per cent CI 48 to 85 per cent).
These results support that it is feasible to use a pragmatic study design to study the comparative effectiveness of balanced versus 0.9 per cent saline fluid resuscitation for paediatric septic shock.
Collaborators
The PROMPT Bolus study is an international randomised controlled trial enrolling participants in Australia, New Zealand, Canada, and the United States of America.
The PROMPT Bolus study is being conducted as a collaboration between the Paediatric Research in Emergency Departments International Collaborative (PREDICT) Network, the Pediatric Emergency Care Applied Research Network (PECARN) and the Pediatric Emergency Research Canada (PERC) research network.
Funding
The PROMPT Bolus study is funded through the Medical Research Future Fund (MRFF) International Clinical Trial Collaborations (ICTC).
Contact us
PRoMPT BOLUS Study
Murdoch Children's Research Institute
The Royal Children's Hospital
50 Flemington Road
Parkville VIC 3052
Australia
Email: [email protected]